Outbreaks with antibiotic-resistant pathogens are occurring in hospital COVID-19 units, primarily caused by multidrug-resistant organisms (MDROs) that are hard to eradicate from the patient environment, a Centers for Disease Control and Prevention (CDC) investigator reports.

Arjun Srinivasan, MD, associate director for Healthcare Associated Infection Prevention Programs, recently updated the situation using data from more than 1,500 CDC sentinel hospitals.

The CDC has responded to at least 20 outbreaks of resistant pathogens in hospital COVID-19 units since April 2020, he said at a meeting of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria.

“The outbreaks were caused by a variety of pathogens, especially ones with a proclivity for environmental contamination like Acinetobacter and Candida auris,” Srinivasan said. “They have generally been caused by challenges to infection control best practices. The outbreaks have been terminated with reinforcement of infection control, but there is concern for the longer-term implications in the regions where these outbreaks have occurred.”

The data on overall antibiotic use during the pandemic continue to show increases in the use of azithromycin and ceftriaxone in both hospitals and nursing homes. This usage appears to correspond with spikes in SARS-CoV-2. An analysis of antibiotic use at the individual hospital level shows more use of broader agents, such as piperacillin and tazobactam, compared to 2019, he said. Perhaps this is a reflection of increased patient acuity. Outpatient antibiotic prescribing remains at historic lows because outpatient visits still are well below normal.

Overall, there is no “clear sign” during the pandemic that hospitalized patients with SARS-CoV-2 infection are more susceptible to MDROs than patients with other viral infections, he said.

“However, the confluence of circumstance we see with COVID — longer lengths of stay, high illness acuity, and large patient volume — does create opportunities for the development and spread of resistant pathogens,” Srinivasan said. “So, it comes as no surprise that we have seen several outbreaks of antibiotic resistant organisms in COVID-19 units. Similarly, we’ve seen increases in some hospital-resistant infections — like MRSA (methicillin-resistant Staphylococcus aureus).”

The findings underscore the importance of “ensuring the continuity” of infection prevention and antibiotic stewardship programs, he added.

“The last thing we want to see is a patient survive COVID only to succumb to another infection,” he said.

‘Old Habits Die Hard’

Antibiotic misuse is a longstanding problem, typically involving the unnecessary use of drugs on pathogens. This kills off the susceptible bacteria while those with a natural resistance persevere. A CDC study covering antibiotic use before the pandemic found that clinical practices frequently deviate from recommendations in terms of selection and duration.1

“In this cross-sectional study of 1,566 patients at 192 hospitals, antimicrobial use deviated from recommended practices for 55.9% of patients who received antimicrobials for community-acquired pneumonia (CAP) or urinary tract infection (UTI) present at admission or who received fluoroquinolone or intravenous vancomycin treatment,” the authors found.

Overall, treatment was unsupported for 876 (55.9%) of the 1,566 patients; 110 (27.3%) of the 403 who received vancomycin; 256 (46.6%) of the 550 who received fluoroquinolones; 347 (76.8%) of the 452 with a diagnosis of UTI, and 174 (79.5%) of the 219 with a diagnosis of CAP.

Hospital Infection Control & Prevention (HIC) sought further comment on these findings from Lauri Hicks, MD, director of the CDC Office of Antibiotic Stewardship. This interview has been edited for length and clarity.

HIC: Can you comment on your overall findings that antimicrobial use deviated from recommended practices for 55.9% of patients?

Hicks: A prevalence survey upon which this analysis was based was conducted in 2015 and establishes a baseline assessment of antibiotic prescribing quality for four common prescribing scenarios in hospitals. The analysis identified several opportunities for improvement. [The] CDC estimates that more than half of antibiotics prescribed in hospitals for these prescribing events were not consistent with recommended prescribing practices. The most striking example is that there were likely opportunities to improve prescribing for nearly 80% of hospitalized patients with community-acquired pneumonia.

Antibiotics were often prescribed for too long, when there was no clinical indication, or the antibiotic selected didn’t follow treatment guidelines. Despite these findings, there are reasons to be optimistic. [The] CDC and [its] partners are working together to improve antibiotic use, and significant progress has been made since 2015. In 2019, 89% of U.S. hospitals met all seven of [the] CDC’s Core Elements of Hospital Antibiotic Stewardship Programs, compared to 48% in 2015. [The] CDC has also received antibiotic use data from more than 2,000 hospitals through [the] CDC’s National Safety Network (up from 120 hospitals in 2015).

HIC: Just to clarify, why were fluroquinolones and intravenous vancomycin included as metrics? We know the former is thought to drive Clostridium difficile infections and the latter is considered among the last-line drugs against MRSA. Were you essentially determining how often these drugs are administered inappropriately?

Hicks: Fluoroquinolones and vancomycin are important antibiotics that are among the most common antibiotics prescribed for hospitalized patients, and they are often prescribed inappropriately. Among patients prescribed fluoroquinolones, antibiotic prescribing was not supported for 46.5% of patients. Most patients for whom fluoroquinolone treatment was unsupported received at least eight days of treatment for lower respiratory, abdominal, or gastrointestinal infections without lab results confirming the presence of infection. Fluoroquinolones are used for a wide range of infections in the hospital and in the outpatient setting. Due to serious side effects associated with fluoroquinolone antibiotics, many experts recommend using alternative antibiotics when possible.

Among patients prescribed intravenous vancomycin, prescribing was not supported for 27.3% of patients. This appears to be most commonly due to continuation of IV vancomycin in patients who did not appear to require it. This includes patients with cultures positive for pathogens susceptible to penicillin, ampicillin, or oxacillin and without a severe or unspecified penicillin allergy. IV vancomycin should not typically be used for routine infections that can be treated more effectively with other antibiotics. IV vancomycin is an important tool for treating infections due to resistant bacteria, such as MRSA.

HIC: You note that one example of an opportunity for improvement suggested by the analysis is excessive treatment duration, which was the most common reason for unsupported CAP treatment. You said further study is needed, but can you comment on some of the drivers of this and ways hospitals can halt treatment at appropriate intervals?

Hicks: Despite changes to treatment guidelines recommending five days of antibiotic therapy for most patients with [CAP], clinicians tend to use longer courses of seven or 10 days that were recommended in earlier guidelines. The adage “old habits die hard” applies here. Once a behavior is ingrained, it can be hard to change a clinician’s practice. Behavioral change strategies are needed to address these practices.

Antibiotic stewardship program interventions, such as prospective audit and feedback to provide clinicians feedback on their performance and facility-specific treatment recommendations, are the keys to changing these practices. Antibiotic stewardship staff can also provide recommendations to de-escalate or stop therapy when it’s no longer needed. Our findings reinforce the need for the shortest effective duration of therapy and re-assess the need for antibiotic therapy when results of diagnostic testing become available. [The] CDC also recommends stewardship programs establish a process to review antibiotic therapy prior to hospital discharge to reduce unnecessary antibiotic use and optimize patient safety.

Reference

  1. Magill SS, O’Leary E, Ray SM, et al. Assessment of the appropriateness of antimicrobial use in US hospitals. JAMA Netw Open 2021;4:e212007.